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Author(s): Christian Sonne, Ursula Siebert, Katharina Gonnsen, Jean-Pierre Desforges, Igor 
Eulaers, Sara Persson, Anna Roos, Britt-Marie Bäcklin, Kaarina Kauhala, Morten 
Tange Olsen, Karin C. Harding, Gabriele Treu, Anders Galatius, Emilie Andersen-
Ranberg, Stephanie Gross, Jan Lakemeyer, Kristina Lehnert, Su Shiung Lam, Wanxi 
Peng and Rune Dietz 
 
Title: Health effects from contaminant exposure in Baltic Sea birds and marine mammals: 
A review 
Year: 2020 
Version: Published version 
Copyright:   The Author(s) 2020 
Rights: CC BY 4.0 
Rights url: http://creativecommons.org/licenses/by/4.0/ 
 
Please cite the original version: 
Sonne C., Siebert U., Gonnsen K., Desforges J.-P., Eulaers I., Persson S., Roos A., Bäcklin B.-M., 
Kauhala K., Tange Olsen M., Harding K.C., Treu G., Galatius A., Andersen-Ranberg E., Gross S., 
Lakemeyer J., Lehnert K., Shiung Lam S., Peng W., Dietz R. (2020). Health effects from contaminant 
exposure in Baltic Sea birds and marine mammals: A review,Environment International 139, 
105725. https://doi.org/10.1016/j.envint.2020.105725. 
Contents lists available at ScienceDirect
Environment International
journal homepage: www.elsevier.com/locate/envint
Health effects from contaminant exposure in Baltic Sea birds and marine
mammals: A review
Christian Sonnea,b,⁎, Ursula Siebertc, Katharina Gonnsenc, Jean-Pierre Desforgesa, Igor Eulaersa,
Sara Perssond, Anna Roosd, Britt-Marie Bäcklind, Kaarina Kauhalae, Morten Tange Olsenf,
Karin C. Hardingg, Gabriele Treuh, Anders Galatiusa, Emilie Andersen-Ranbergi, Stephanie Grossc,
Jan Lakemeyerc, Kristina Lehnertc, Su Shiung Lamb,j, Wanxi Pengb, Rune Dietza
a Department of Bioscience, Arctic Research Centre (ARC), Aarhus University, Faculty of Science and Technology, Frederiksborgvej 399, PO Box 358, DK-4000 Roskilde,
Denmark
bHenan Province Engineering Research Center for Biomass Value-added Products, School of Forestry, Henan Agricultural University, Zhengzhou CN-450002, China
c Institute for Terrestrial and Aquatic Wildlife Research, University of Veterinary Medicine Hannover, Werftstr. 6, 25761 Büsum, Germany
d Swedish Museum of Natural History, Department of Environmental Research and Monitoring, Frescativägen 40, SE–104 05 Stockholm, Sweden
eNatural Resources Institute Finland, Luke. Itäinen Pitkäkatu 4 A, FI-20520 Turku, Finland
f Evolutionary Genomics, Natural History Museum of Denmark, Department of Biology, University of Copenhagen, Øster Voldgade 5-7, DK-1350 Copenhagen K, Denmark
g Department of Biological and Environmental Sciences, University of Gothenburg, Box 463, 25 SE-405 30 Gothenburg, Sweden
hGerman Environment Agency, Section Chemicals, Wörlitzer Platz 1, 06844 Dessau-Roßlau, Germany
iDepartment of Veterinary Clinical Sciences, University of Copenhagen, Faculty of Health, Dyrlægevej 16, 1870 Frederiksberg C, Denmark
j Pyrolysis Technology Research Group, Institute of Tropical Aquaculture and Fisheries (Akuatrop) & Institute of Tropical Biodiversity and Sustainable Development (Bio-D
Tropika), Universiti Malaysia Terengganu, MY-21030 Kuala Terengganu, Terengganu, Malaysia
A R T I C L E I N F O
Handling Editor: Dr. Da Chen
Keywords:
PCBs
Polychlorinated biphenyls
Baltic Sea
POPs
Persistent organic pollutants
Organochlorine pesticides
OCP
Exposure
Biological effects
Contaminants
A B S T R A C T
Here we review contaminant exposure and related health effects in six selected Baltic key species. Sentinel
species included are common eider, white-tailed eagle, harbour porpoise, harbour seal, ringed seal and grey seal.
The review represents the first attempt of summarizing available information and baseline data for these bio-
monitoring key species exposed to industrial hazardous substances focusing on anthropogenic persistent organic
pollutants (POPs). There was only limited information available for white-tailed eagles and common eider while
extensive information exist on POP exposure and health effects in the four marine mammal species. Here we
report organ-tissue endpoints (pathologies) and multiple biomarkers used to evaluate health and exposure of key
species to POPs, respectively, over the past several decades during which episodes of significant population
declines have been reported. Our review shows that POP exposure affects the reproductive system and survival
through immune suppression and endocrine disruption, which have led to population-level effects on seals and
white-tailed eagles in the Baltic. It is notable that many legacy contaminants, which have been banned for
decades, still appear to affect Baltic wildlife. With respect to common eiders, changes in food composition,
https://doi.org/10.1016/j.envint.2020.105725
Received 30 September 2019; Received in revised form 29 March 2020; Accepted 4 April 2020
Abbreviations: ∑PCB14, Sum of 14 CB congeners; AHR, Aryl hydrocarbon receptor; ARNT, Aryl hydrocarbon receptor nuclear translocator; BSDC, Baltic Seal Disease
Complex; CB-118, Chlorinated biphenyl-118; CB-149, Chlorinated biphenyl-149; CB-180, Chlorinated biphenyl-180; CYP-450, Cytochrome P450; DDE,
Dichlorodiphenyldichloroethylene; DDT, Dichlorodiphenyltrichloroethane; DNA, Deoxyribonucleic acid; FT3, Free triiodothyronine; FT4, Free Thyroxine; GST,
Glutathione S-transferase; H10N7, Avian influenza virus; Hg, Mercury; HSP70, Heat shock protein 70; MeHg, Methylmercury; mRNA, Messenger RNA; PBDE,
Polybrodminated diphenyl ethers; PCBs, Polychlorinated biphenyls; PDV, Phocine distemper virus; PFAS, Per and polyfluoroalkyl substances; POPs, Persistent
organic pollutants; PPARα, Transcription factor peroxisome proliferator-activated receptor; p,p’-d, p,p′-Dichlorodiphenyldichloroethane; p,p’-DDE, p,p′-
Dichlorodiphenyldichloroethylene; p,p’-DDT, p,p’-Dichlorodiphenyltrichloroethane; TT3, Total Triiodothyronine; TT4, Total Thyroxine; TTR, Transthyretin; VSI,
Virtual Special Issue
⁎ Corresponding author at: Department of Bioscience, Arctic Research Centre (ARC), Aarhus University, Faculty of Science and Technology, Frederiksborgvej 399,
PO Box 358, DK-4000 Roskilde, Denmark.
E-mail addresses: cs@bios.au.dk (C. Sonne), Ursula.siebert@tiho-hannover.de (U. Siebert), Katharina.Gonnsen@tiho-hannover.de (K. Gonnsen),
jpd@bios.au.dk (J.-P. Desforges), ie@bios.au.dk (I. Eulaers), sara.persson@nrm.se (S. Persson), anna.roos@nrm.se (A. Roos),
britt-marie.backlin@nrm.se (B.-M. Bäcklin), kaarina.kauhala@luke.fi (K. Kauhala), morten.olsen@bio.ku.dk (M. Tange Olsen),
karin.harding@bioenv.gu.se (K.C. Harding), Gabriele.Treu@uba.de (G. Treu), agj@bios.au.dk (A. Galatius), emilie.ranberg@sund.ku.dk (E. Andersen-Ranberg),
Stephanie.gross@tiho-hannover.de (S. Gross), Jan.Helge.Carl.Lakemeyer@tiho-hannover.de (J. Lakemeyer), Kristina.Lehnert@tiho-hannover.de (K. Lehnert),
lam@umt.edu.my (S.S. Lam), rdi@bios.au.dk (R. Dietz).
Environment International 139 (2020) 105725
0160-4120/ © 2020 The Authors. Published by Elsevier Ltd. This is an open access article under the CC BY license 
(http://creativecommons.org/licenses/BY/4.0/).
T
quality and contaminant exposure seem to have population effects which need to be investigated further,
especially during the incubation period where the birds fast. Since new industrial contaminants continuously
leak into the environment, we recommend continued monitoring of them in sentinel species in the Baltic,
identifying possible effects linked to climate change, and modelling of population level effects of contaminants
and climate change.
1. Introduction
Determining the health status of wildlife including marine mammals
is difficult as they are rarely observed and handled (Dietz et al., 2019;
Letcher et al., 2010). Physiological monitoring and detection of altered
physical states may be evaluated at various biological scales from the
molecular to the individual, population and community, which evi-
dently provide different measures of reproductive capacity and degree
of change (Sonne, 2010). The strength in using a combination of organ-
tissue endpoints (pathologies) and biomarkers lies in the ultimate
provision of a comprehensive health status and linkages to external
stressors (Sonne, 2010). This is the basis for an evaluation of population
health and exposure to environmental stressors such as persistent or-
ganic pollutants (POPs) that may lead to significant population declines
(Dietz et al., 2019).
The Baltic ecosystem has undergone drastic changes over the past
century due to anthropogenic chemical stress caused by POPs. As is
often the case, these changes have been most notably documented in
selected wildlife species such as grey seals (Halichoerus grypus), ringed
seals (Pusa hispida) and white-tailed eagles (Haliaeetus albicilla). These
species have undergone massive population declines with POPs ex-
posure as the major force behind the reduced health of Baltic wildlife
and ecosystems. While the individual-level effects of POPs have been
studied in Baltic sentinel species such as ringed and grey seal, harbour
porpoise and white-tailed eagles (Roos et al., 2012; Helander et al.,
2008; Siebert et al., 2006, 2007), little effort has been made to quantify
population level effects. Rodriguez-Estival and Mateo (2019) have
shown that one of the major challenges in wildlife ecotoxicology
including marine mammals is to establish strong links between ex-
posure to anthropogenic chemicals and adverse health effects. To
manage and conserve wildlife populations, it is therefore crucial to
quantify how pollution measured at the individual level propagates to
population-level effects through impacts on mortality and reproduction,
but also effects on fertility, energy allocation, immune and endocrine
functioning (Harding and Härkönen, 1999; Sundqvist et al., 2012;
Harding et al., 2015). This also requires a combination of in vitro dose-
response studies as well as in vivo studies of key species in the Baltic as
reference populations from pristine areas such as the Arctic when
possible.
In the present paper, we review health effects from pollution on
Baltic key species over the past seven decades including ringed seal,
grey seal, harbour seal, harbour porpoises, white-tailed eagle and
common eider (Fig. 1). Information about health effects in the seal
species was comprehensive while fewer investigations are reported on
harbour porpoise, white-tailed eagles and common eiders that spend
most of their time in the Baltic despite migration out of the area is
happening after end breeding season (Kjellén and Roos, 2000; Swennen
et al., 1989). These species were selected as they represent sentinel high
trophic indicator species in the Baltic regions that for decades have
been used to biomonitor the environment. Due to the long-term mon-
itoring over 7 decades, the Baltic Sea is an ideal ecosystem to study and
related findings are extrapolated globally and used in the monitoring
and assessment of for example the Arctic region (Dietz et al., 2019). The
effects from other stressors such as infectious diseases on Baltic sentinel
species is reported elsewhere in this virtual special issue (VSI) of En-
vironment International.
Fig. 1. Distribution and study sites of the six species included in the present review. Please also visit: http://www.helcom.fi/baltic-sea-trends/biodiversity/red-list-
of-species/red-list-of-marine-mammals/.
C. Sonne, et al. Environment International 139 (2020) 105725
2
2. Literature survey
From our own experience in the field, we identified and searched for
environmental contaminants that are known to biomagnify in wildlife.
In addition to these, we searched for effects from contaminants on
specific organ-tissue health endpoints. We used ScienceDirect, PubMed,
Google, Google Scholar, ISI Web of Knowledge/Web of Science and
Springer Link to locate the peer-reviewed scientific articles and reports,
using the following key words (either alone or in combination): eider,
white-tailed eagle, harbour seal, grey seal, ringed seal, harbour por-
poise, contaminants, POPs; persistent organic pollutants; PCBs, poly-
chlorinated biphenyls, mercury, syndrome, organ, histopathology,
bone, reproductive organs, reproduction, vitamins, hormones, endo-
crine system, cytokines, lymphocyte proliferation test, skeletal, bone
density, immunology, immune system, skull, cancer, oxidative stress,
DNA and CYP-450 (Table 1 and 2). We also used educational and sci-
entific textbooks and references cited herein, apart from the selected
articles retrieved by the above-mentioned efforts. Although we at-
tempted to be systematic within the scope of the review, we acknowl-
edge that this is not an exhaustive representation of all information that
may exist in the scientific literature.
3. The baltic seal disease complex
The Baltic Sea is a unique marine region with low salinity while
exposed to many anthropogenic factors such as industry activities,
transport, cargo, military and fishing ships. A widely distributed pa-
thological disease syndrome caused by exposure to POPs is reported
among grey seals and ringed seals in the Baltic Sea, North Sea and
German Bight from 1977 to 1983 and it may still occur to a lesser extent
(Bergman and Olsson, 1985; Helle, 1980; Helle et al., 1976a; 1976b).
Table 2 summarizes the POPs induced Baltic Seal Disease Complex
(BSDC) and links each health effect to the sentinel species and shows
whether it causes effects on the individual or population level or both.
The complex included hyperplasia of adrenal glands, reduced bone
density and skin changes, which altogether indicate elevated produc-
tion of cortisol due to extreme physiological stress (Table 2). Elevated
concentrations of PCBs (polychlorinated biphenyls) and p,p’-DDT (di-
chlorodiphenyltrichloroethane) were detected in these animals, and the
chemicals were identified as the cause of the observed syndrome,
closely resembling endocrine disruption of iatrogenic (caused by ex-
ternal factors) similar to Cushing’s in dogs, or due to multiple chronic
organ lesions secondary to the organochlorine caused lesions (Bergman,
2007; Cohn et al., 2007). The blubber threshold concentrations in seals
at which the BSDC arose was around 100 μg/g lw (∑PCB17 range:
27–390 μg/g lw; DDT [p,p’-DDE, p,p’-DDD and p,p’-DDT] range:
12–970 μg/g lw) being among the highest ever measured in wild
phocids (Table 2) (Jensen et al., 1979; Letcher et al., 2010; Roos et al.,
2012).
The prevalence of occlusions and stenosis of the uterus were as high
as 30% and 70% in grey and ringed seals, respectively. In addition,
tumours in the smooth muscle tissue of the uterine myometrium
(leiomyomas) were found, but only in old grey seals indicative of be-
nign neoplastic changes (Bergman, 1999). Bredhult et al. (2008) gath-
ered material consisting of 257 Baltic grey seal females to study the
statistical relationship between concentrations of PCBs and p,p’-DDT
and leiomyoma from 1973 to 2007 (Table 2). The authors found neo-
plastic changes only in old specimens, 20–40 years of age, and with a
prevalence of 65%. Likewise, skull and claw lesions and renal glomer-
ulopathy (changes in glomerular structure and functioning of the kid-
neys), interstitial nephritis and tubular hyperplasia as well as intestinal
ulcers and arteriosclerosis were reported (Bergman and Olsson, 1985;
Bergman, 1999).
The following text provides an overview of endpoints associated
with exposure to POPs including PCBs and p,p’-DDT used to investigate
the health of Baltic Sea top predators over the past decades, sub-divided
into pathological organ-system changes and biomarkers of exposure.
Fig. 1 shows the distribution and study sites of the species included in
the present review.
4. Ulcers and tumours
Since the 1970's, BSDC in Baltic grey seals have been associated
with impaired reproduction and reduced health with the main causal
factor being exposure to POPs (Table 2) (Bergman, 2007). Most of BSDC
symptoms, especially in the reproductive tract, i.e. uterine occlusions,
leiomyomas and uterine horn stenosis, started to decrease in the early
1990's in the Baltic environment following the reduction of PCB and
p,p’-DDT ban in the mid 1970ies (Bergman, 1999; Bäcklin et al,. 2011).
On the contrary, the prevalence of colonic ulcers in young (1–3 years
Table 1
Literature search strategy for the present review using search machines, taxa and key words. Each taxa was also used as keyword.
Search machines Taxa Keywords
ScienceDirect Harbour seal eider, white-tailed eagle, harbour seal, grey seal, ringed seal, harbour porpoise, contaminants, POPs, persistent organic
pollutants, PCBs, polychlorinated biphenyls, mercury, syndrome, organ, histopathology, bone, reproductive organs,
reproduction, vitamins, hormones, endocrine system, cytokines, lymphocyte proliferation test, skeletal, bone density,
immunology, immune system, skull, cancer, oxidative stress, DNA and Cyp-450
Pubmed Ringed seal eider, white-tailed eagle, harbour seal, grey seal, ringed seal, harbour porpoise, contaminants, POPs, persistent organic
pollutants, PCBs, polychlorinated biphenyls, mercury, syndrome, organ, histopathology, bone, reproductive organs,
reproduction, vitamins, hormones, endocrine system, cytokines, lymphocyte proliferation test, skeletal, bone density,
immunology, immune system, skull, cancer, oxidative stress, DNA and Cyp-450
Google Grey seal eider, white-tailed eagle, harbour seal, grey seal, ringed seal, harbour porpoise, contaminants, POPs, persistent organic
pollutants, PCBs, polychlorinated biphenyls, mercury, syndrome, organ, histopathology, bone, reproductive organs,
reproduction, vitamins, hormones, endocrine system, cytokines, lymphocyte proliferation test, skeletal, bone density,
immunology, immune system, skull, cancer, oxidative stress, DNA and Cyp-450
Google Scholar Harbour porpoise eider, white-tailed eagle, harbour seal, grey seal, ringed seal, harbour porpoise, contaminants, POPs, persistent organic
pollutants, PCBs, polychlorinated biphenyls, mercury, syndrome, organ, histopathology, bone, reproductive organs,
reproduction, vitamins, hormones, endocrine system, cytokines, lymphocyte proliferation test, skeletal, bone density,
immunology, immune system, skull, cancer, oxidative stress, DNA and Cyp-450
ISI Web of Knowledge/WoS White-tailed eagle eider, white-tailed eagle, harbour seal, grey seal, ringed seal, harbour porpoise, contaminants, POPs, persistent organic
pollutants, PCBs, polychlorinated biphenyls, mercury, syndrome, organ, histopathology, bone, reproductive organs,
reproduction, vitamins, hormones, endocrine system, cytokines, lymphocyte proliferation test, skeletal, bone density,
immunology, immune system, skull, cancer, oxidative stress, DNA and Cyp-450
Springer Link Common eider eider, white-tailed eagle, harbour seal, grey seal, ringed seal, harbour porpoise, contaminants, POPs, persistent organic
pollutants, PCBs, polychlorinated biphenyls, mercury, syndrome, organ, histopathology, bone, reproductive organs,
reproduction, vitamins, hormones, endocrine system, cytokines, lymphocyte proliferation test, skeletal, bone density,
immunology, immune system, skull, cancer, oxidative stress, DNA and Cyp-450
C. Sonne, et al. Environment International 139 (2020) 105725
3
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old) grey seals increased significantly from 15% (1977–1986) to 53%
(1987–1996) (Bergman, 1999). These colonic alterations, ulcers and
thickened intestinal walls still occur and are commonly associated with
the parasite Corynosoma spp. Acanthocephala infection (Bergman 1999,
2007). Exposure to POPs leads to immunosuppression across marine
mammal species and may explain the colonic alterations and chronic
infections continuously observed in Baltic grey seals (Bergman, 2007;
Desforges et al., 2016; Jepson et al., 2016).
The prevalence of colonic ulcers also increased in 4–20 years old
grey seals in the Gulf of Bothnia between 1997 and 2006 and their
prevalence is persistently high (Bäcklin et al., 2011; Norrgren et al.
2012). In grey seals in the Gulf of Bothnia investigated from 2002 to
2007, the prevalence of intestinal ulcers increased with age from 24%
(1–3 years old) to 74% (11–20 years old) in hunted males (Bäcklin
et al., 2011). Colonic ulcers were a notable cause of mortality, when
perforating the intestinal wall, especially near the head of the caecum,
opposite the ileocolic orifice (Bergman, 1999). There is only one known
case of intestinal ulceration in non-Baltic grey seals (Baker, 1980). In a
recent study of Atlantic grey seals, no colonic alterations were found
which again support that these types of lesions predominantly affect
Baltic grey seals (Bäcklin et al., 2013; ÓNeill et al. 2002).
5. Reproductive impairment
5.1. Grey seals
The population of grey seals and ringed seals decreased dramati-
cally in the 1960′s and 1970′s in the Baltic Sea due to reproductive
impairment. High hunting pressure and contaminant-induced sterility
of females resulted in a population crash prior to the 1960 s, and
contaminants further hindered population recovery thereafter (Harding
and Härkönen, 1999; Harding et al., 2007). Roos et al. (2012) showed
that the pregnancy in grey seals increased over the period 1990–2010,
while the prevalence of uterine occlusions and stenosis and uterine
tumours decreased. This is an ongoing tendency supported by findings
that the reproductive rate of grey seals is normal at present and that
birth rate in Finnish waters is 88% (mean for 2013–2018, no uterine
occlusions observed) (Kauhala et al., 2017). Today, adult animals only
show minor renal BSDC symptoms due to the relatively low POP levels
(Bäcklin et al., 2013; Bergman et al., 2001). Bergman (1999) reported
on the temporal distribution of the syndrome covering the period
1977–1996 and found that gynaecological pathology had improved
while the concentration of environmental contaminants had decreased
(Bjurlid et al., 2018).
5.2. White-tailed eagles
The Swedish population of white-tailed eagles almost crashed over
the period 1960–1990 due to eggshell thinning and reproductive failure
from egg exposure to p,p’-DDE and ∑PCB22 concentrations of 70–1300
and 260–1500 μg/g lw, respectively (Table 2) (Helander et al., 2002;
Helander et al., 1982). Helander et al. (2008) did a comprehensive
review of the biomonitoring of pollution and health effects in Baltic
white-tailed eagles showing that the Scandinavian subpopulations have
recovered since the 1980's after regulation of the contaminants in-
cluding p,p’-DDT took place (Bignert and Helander, 2015; Helander
et al., 2002; Scharenberg and Struwe-Juhl, 2006). Following the pub-
lications on the collapse of the white-tailed eagle population in the
1960–90's, Roos et al. (2012) reviewed and updated the reproductive
health of white-tailed eagles in the Swedish part of the Baltic for the
period 1990–2010. The analyses showed that the reproduction of
white-tailed eagles increased over the study period and these changes in
reproduction correlated closely with temporal declines in the con-
centrations of PCBs and p,p’-DDT. This further strengthens the causal
association between these chemicals and observed reproductive im-
pairment in seals and eagles in the 1960–1980 s (Bergman, 1999; Roos
et al., 2012). Although PCBs have been consistently detected at higher
levels than p,p’-DDT, p-p’-DDT, they are considered to have less of an
effect on the reproduction of white-tailed eagles compared to p,p’-DDE
(Helander et al., 2002).
6. Skeletal pathology
Pathology of the skeletal system was also a major contributor to the
BSDC. Reports of pathology include fluctuating asymmetry, changes in
bone mineral density, and severe periodontitis and peri-alveolar in-
flammation and disease in ringed and grey seals (Table 2) (Bergman
and Olsson, 1985). Bergman et al. (1992) showed that, by comparing
grey seal skull lesions collected prior to 1950 and after 1960, period-
ontitis with loss of alveolar bone was the highest in the post 1960
period as well as having high concentrations of environmental con-
taminants such as PCBs and p,p’-DDT. Again, the lesions were similar to
those in hyperadrenocorticism and the major cause being POPs was
supported by a study of Baltic harbour seals by Mortensen et al. (1992).
Mortensen et al. (1992) showed that the highest prevalence of alveolar
bone loss and exostosis occurred in Baltic seals compared to those from
the Swedish west coast which is generally less polluted.
Lind et al. (2003) reported that bone mineral density increased with
increasing PCB concentration. That BMD is increasing with increasing
PCB concentrations suggests that bone rebuilding is undergoing
changes due to endocrine disruption which does not necessarily mean
better quality or stronger bone but rather an indication of impaired
bone quality. This impaired quality is reflected in decreased bone
bending strength and collagen mass. The individual effects are ob-
viously a risk of fractures and osteoporosis as well as mandibular
functioning i.e. chewing of food (Sonne, 2010).
Schandorff (1997) and Zakharov and Yablokov (1990) reported on
the stability of foetal and neonatal development reflected by metric and
non-metric (foramina) asymmetry of 361 harbour seal skulls from the
Baltic region. The study also analysed the prevalence of exostosis,
periodontitis, and loss of alveolar bone structure. The study showed
that a reduction in the developmental stability (i.e. increase in fluctu-
ating asymmetry and prevalence of pathology) was the highest, with
high levels of environmental contaminants in the Baltic Sea, following
World War II. The developmental stability increased and pathology
decreased in the period after 1988 and this was likely associated with
decreasing concentrations of environmental contaminants in the Baltic
region. Using 380 skulls and 141 mandibles in harbour seals from the
waters surrounding Denmark, Pertoldi et al. (2018) showed a sig-
nificant increase of pathological lesions from 1981 to 2014, and that
skulls with lesions had higher asymmetry. One hypothesis is that these
increasing trends could be linked to immune suppression from cumu-
lative stress of multiple factors such as increasing PFAS (per and
polyfluoroalkyl substances) concentrations and decreases in the quality
and quantity of food resources (Sonne, 2010).
7. Immune system
7.1. Harbour seals
A well-functioning immune system is pivotal for animal health as it
protects against infectious diseases and cancerous growths. The
southern Baltic and neighbouring seas have been the site of major viral
outbreaks in harbour seals, occurring in 1988, 2002 and 2014. Here,
mass mortalities of tens of thousands of individuals, mostly at the Baltic
border towards the North Sea, were caused by phocine distemper virus
(PDV) and Avian Influenza Virus (H10N7) (Harding et al., 2002;
Härkönen, 2006; Zohari et al., 2014; Bodewes et al., 2015). Immune
suppression owing to contaminant exposure was suggested as an im-
portant factor adding to the poor environmental status of Baltic seals,
and a captive feeding study with harbour seals was carried-out to in-
vestigate this linkage (Ross et al., 1996) (Table 2). Feeding seals with
C. Sonne, et al. Environment International 139 (2020) 105725
5
fish from contaminated Baltic waters resulted in significant immune
suppression relative to seals fed with less contaminated fish, based on
diminished T-cell function, delayed-type hypersensitivity, antibody re-
sponses, and natural killer cell activity (Ross et al., 1996). This feeding
study was the first to show conclusively that environmental con-
taminants could significantly modulate the immune system of exposed
marine mammals and established an effect threshold at 17 µg g−1 lw
PCBs in blubber.
To complement the study by Ross et al. (1996) that focused on
POPs, blood samples from Baltic marine mammals were used to isolate
immune cells for in vitro dose-response studies using metals. Nickel,
chromium, aluminium and lead stimulated lymphocyte proliferation in
harbour seals while cadmium and different forms of mercury caused
significant immune suppression (Das et al., 2008; Kakuschke et al.,
2005, 2009). A recent study evaluated the in vitro immune responses
from various marine mammal species against a wide range of con-
centrations of a realistic POPs mixture extracted from marine mammal
blubber (Desforges et al. 2017a). This study showed clear immune
suppressive effects of the POP mixture in several species of cetaceans
and seals, and revealed effect thresholds much lower than observed
when testing individual contaminants. In addition, Desforges et al.
(2016) reviewed the literature including seals from the Baltic and
showed that threshold levels for suppression of lymphocyte prolifera-
tion is 0.001–10 µg/g for PCBs, 0.002–1.3 µg/g for Hg and
0.009–0.06 µg/g for MeHg and 0.1–2.4 µg/g for cadmium in several
pinniped and cetacean species. Similarly, thresholds for suppression of
phagocytosis were 0.6–1.4 and 0.08–1.9 µg/g for PCBs and mercury,
respectively. Altogether, these studies are timely and have important
implications for future risk assessments as highlighted by Lehnert et al.
(2018).
7.2. Harbour porpoise
Studies of the immune system in Baltic predators are either in vivo
examinations of immune health and disease burden or in vitro techni-
ques to investigate the effects from specific contaminant compounds
and groups. For in vivo studies, necropsy findings from Baltic harbour
porpoises have provided evidence that regional contamination of the
environment with POPs and metals (e.g. mercury) is associated with
increased incidence of bacterial and parasite infections (Wunschmann
et al., 2001). This also included pathology of lymphoid and other in-
fected tissues as revealed through comparison with specimens from less
contaminated Arctic regions (Beineke et al., 2005; 2007; Siebert et al.,
1999).
Immunological investigations of animals from German Baltic waters
held in rehabilitation centres have provided opportunities to assess new
diagnostic tools potentially useful for wildlife health assessments. These
molecular tools have been used in free-ranging Baltic marine mammals
to link contaminant stress to cytokine gene expression (Beineke et al.
2007; Lehnert et al., 2014; Routti et al. 2010; Weirup et al. 2013). Heat
shock protein (HSP70) and receptors related to POP exposure including
AHR (aryl hydrocarbon receptor), ARNT (aryl hydrocarbon receptor
nuclear translocator) and PPARα (transcription factor peroxisome
proliferator-activated receptor) have also been used (Lehnert et al.
2014). A significant decrease in xenobiotic markers AHR and ARNT
transcription was found in grey seal pups after weaning rehabilitation
due to POP exposure during lactation reinforced by maternal fasting
and adipose tissue mobilization (Lehnert et al. 2014).
8. Thyroid hormones
8.1. Ringed and grey seals
Hormones are produced by endocrine glands and play an important
role as signal compounds in the thalamic-hypothalamic-pituitary
pathway controlling physiological processes (Letcher et al. 2010; Sonne
2010). Routti et al. (2010) compared the status of thyroid hormones of
ringed seals from the Baltic Sea with the less polluted Svalbard north of
Norway. The POP levels of the Baltic seals were tenfold higher than in
those from the Arctic (Routti et al. 2008a, 2009). The contaminated
Baltic seals had higher plasma concentrations of free triiodothyronine,
and higher hepatic mRNA expressions of deiodinase-I and thyroid
hormone receptor β. The ratio of free and total T3 were also positively
correlated to contaminant metabolites, suggesting that POPs interacted
with transport proteins like transthyretin (TTR) in Baltic ringed seals
that may affect both the imuune and reproductive system as well as
bone disease (Routti et al. 2010). Likewise, Sørmo et al. (2005) ex-
amined thyroid hormones in Baltic grey seal pups from various areas in
relation to organochlorine pollutants. The investigations showed no
differences in plasma concentrations of FT4 and TT4 between the Baltic
and Arctic seals. However, there seems to be a modifying effect on the
transformation of thyroxine to triiodothyronine. The low TT3 and FT3
in plasma were noticeable in Baltic grey seal pups. The most influential
pollutants identified in that study were CB-118, CB-149, CB-180,
∑PCB14 and p,p’-DDT.
8.2. Harbour porpoises
A multivariate statistical analysis showed that the increase of con-
nective tissue in the thyroid of harbour porpoises was mainly correlated
to the higher PCB, PBDE, p,p’-DDE and p,p’-DDT concentrations in the
blubber (Das et al. 2006). Replacement of thyroid follicles by con-
nective tissue results in severe impairment of thyroid function, which
supports the hypothesis that thyroid fibrosis may be caused by con-
taminants (Schumacher et al. 1993). In these studies, it was postulated
that thyroid colloid depletion and fibrosis in harbour seals, and to a
lesser degree in harbour porpoises, may be linked to high tissue con-
centrations of PCBs. The study by Das et al. (2006) examined thyroid
glands from 57 harbour porpoises and showed statistical relationships
between thyroid fibrosis and various organochlorines and PBDEs;
however, the pathways for the toxicity of environmental contaminants
could not be determined.
9. Vitamins
Vitamins are essential compounds for the proper functioning of
physiological processes. Vitamin D is of endogenous as well as dietary
origin while vitamins A, C and E are purely dietary antioxidants (Canter
et al. 2007). The vitamins most often included in wildlife studies are
vitamins A, E and D (Routti et al. 2005). Analysis of vitamins in Baltic
ringed seals and grey seals were collected in the period 1996–1998 and
compared to reference seals from Svalbard (ringed seals) and Canada
(grey seals) (Table 2) (Nyman et al. 2003). Vitamin A and E levels were
found to be reliable biomarkers of exposure for exposure to PCBs and
p,p’-DDT based on significant negative correlations. A later follow-up
study found that Baltic seals had upregulated hepatic mRNA expression
of the vitamin A receptor (retinoic acid receptor α) and lower plasma
vitamin A levels (retinol) as compared to the lesser contaminated Arctic
population (Routti et al. 2010).
The biomagnification of contaminants (PCBs and p,p’-DDT) as well
as vitamins A and E in the food web of grey and ringed seals in the Bay
of Bothnia were also studied and compared with reference seals from
more pristine regions of Svalbard and Canada (Routti et al. 2005). PCBs
were higher in grey seals than ringed seals, while p,p’-DDT was similar
in both species in the Baltic Sea. Routti et al. (2008a) suggested that the
bone lesions (and reproductive failures) seen in Baltic seals during the
period of high environmental contamination in the Baltic, was likely
associated with reduced concentrations of vitamin D and increased
concentrations of thyroid hormones. Increased cortisol and disruption
of circulating sex steroids have also been linked to bone absorption,
pathology and changes in bone density (Letcher et al. 2010; Sonne
2010).
C. Sonne, et al. Environment International 139 (2020) 105725
6
9.1. Vitamin B
Thiamine (Vitamin B1) deficiency has been suggested as a factor in
the mortality of marine birds in the Baltic. Sylvander et al. (2013) re-
ported decreasing levels of thiamine with increasing trophic level
across species in the Baltic Sea ecosystem (Table 2). A disease named
‘paralysis syndrome’ caused sea bird population declines around the
Baltic Sea between 1990 and 2010. It was characterized by paralysis of
the wings, followed by complete paralysis and death of the birds (Balk
et al. 2009). Sonne et al. (2012) reviewed these cases and concluded the
cause to be a multifactorial disease complex involving exposure to en-
vironmental contaminants e.g. mercury, lead, PCBs etc. as well as
toxins, vitamin deficiencies and may be infectious diseases.
The Baltic Sea population of common eiders has declined dramati-
cally during the last two decades and changes in food web dynamics
and contaminant exposure affecting survival and reproduction are
likely some of the causes. Morner et al. (2017) proposed that the decline
could be due to thiamine deficiency being one of the multiple causes as
discussed further by Sonne et al. (2012). Recently, widespread episodic
thiamine (Vitamin B1) deficiency has been demonstrated in feral birds
and suggested to contribute significantly to the declining populations.
The decline of the common eider population in the Baltic is paralleled
by high mortality of the ducklings a few days after hatch, partly owing
to thiamine deficiency and probably thereby associated abnormal be-
haviour resulting in high gull and white-tailed eagle predation (Morner
et al. 2017). Together with exposure to environmental contaminants
and also limited food access, these factors likely affect the population
declines and dynamics of the Baltic common eider (Sonne et al., 2012;
Garbus et al. 2018, 2019).
10. DNA lesions and liver enzymes
Fensted et al. (2016a, 2016b) investigated oxidative stress and DNA
double-strand breaks in Baltic and Svalbard eider ducks and showed
that Baltic eiders had higher concentrations of antioxidants, suggesting
a possible upregulation in response to oxidative stressors such as PCBs
(Table 2). Importantly, they hypothesize that such upregulation may
incur considerable energetic costs. The analyses of DNA breaks did not
reveal a link to POPs, however, positive correlations were found with
mercury. Environmental contaminants as well as endogenous com-
pounds undergo biotransformation in the body, which can lead to
bioactivation of metabolites and/or facilitated excretion. Bio-
transformation of contaminants involves xenobiotic-metabolizing Phase
I (cytochrome P450; CYP) and conjugating Phase II enzymes (glu-
tathione S-transferase; GST). Routti et al. (2008b) investigated con-
centration of PCBs, liver phase I and 11 enzymes and formation of PCB
metabolites in ringed seals from the Baltic Sea and the less con-
taminated Svalbard peninsula (Table 2). The analyses showed that PCBs
upregulated Phase I enzymes and GST activities, increasing the bio-
transformation of specific PCBs. Altogether, such inductions could lead
to increases in the concentrations of bioactive PCB metabolites and to
metabolism of endogenous hormones causing possible endocrine dis-
ruption.
11. Considerations
Given the severity of contaminant exposure and other stressors in
the Baltic, pathological organ-system changes and biomarkers of ex-
posure are of particular importance to detect population level effects.
This is in contrast to the Arctic and other regions where the impacts of
stress may be more subtle and severe population declines due to con-
taminant exposure have not been reported. It is notable that many le-
gacy contaminants, which have been banned for decades, still appear to
affect Baltic wildlife. Given the multiple stressors in the Baltic Sea, new
techniques are needed to integrate various health impacts and extend
these to the population level and reported elsewhere in the Special Issue
(Cervin et al., in review; Silva et al., in review). Modelling approaches
utilizing bioenergetics and individual and agent based models are re-
quired to provide the basis for extrapolating effects from the molecular
to the individual and eventually the population level (Desforges et al.
2017b, 2018; Martin et al. 2013) The combined effect from slightly
reduced fecundity, increased suceptibiilty to infectious disease and
anthropogenic stressors such as by-catches can bring the slowly re-
covering Baltic marine mammal populations to a new area of popula-
tion declines and near extinction as accompanying studies in the cur-
rent Special Issue illustrate (Cervin et al., in review; Silva et al., in
review). With respect to common eiders, little information is available
on contaminants exposure and population effects and that should be
investigated further especially during incubation where the birds fast
and climate change seem to limit food resources further prior to start of
incubation (Balk et al. 2009; Garbus et al. 2018, 2019; Sonne et al.,
2012). In relation to that, food-web changes and quality of eider prey
should be mapped, as energetics is a major factor for eider duck re-
production. With respect to white-tailed eagles, and despite the Baltic
population having re-established itself, it is still important to monitor
the health, reproduction and population dynamics of this important
sentinel apex predator.
12. Conclusions
Our review shows that POP exposure affects the reproductive
system and survival through immune suppression and endocrine dis-
ruption which have led to population-level effects on seals and white-
tailed eagles in the Baltic. It is notable that many legacy contaminants,
which have been banned for decades, still appear to affect Baltic
wildlife. With respect to common eiders, changes in food composition,
quality and contaminant exposure seem to have population effects
which need to be investigated further especially during incubation
where the birds fast. Since new industrial contaminants continuously
leak into the environment, we recommend to continue the monitoring
of sentinel species in the Baltic and to continue model development to
also include the possible effects linked to climate change.
CRediT authorship contribution statement
Christian Sonne: Conceptualization, Methodology, Writing - ori-
ginal draft, Writing - review & editing, Data curation. Ursula Siebert:
Writing - review & editing. Katharina Gonnsen: Writing - review &
editing. Jean-Pierre Desforges: Writing - review & editing. Igor
Eulaers: Writing - review & editing. Sara Persson: Writing - review &
editing. Anna Roos: Writing - review & editing. Britt‐Marie Bäcklin:
Writing - review & editing. Kaarina Kauhala: Writing - review &
editing. Morten Tange Olsen: Writing - review & editing. Karin
Harding:Writing - review & editing. Gabriele Treu:Writing - review &
editing. Anders Galatius: Writing - review & editing. Emilie
Andersen-Ranberg: Writing - review & editing. Stephanie Gross:
Writing - review & editing. Jan Lakemeyer:Writing - review & editing.
Kristina Lehnert: Writing - review & editing. Su Shiung Lam: Writing
- review & editing. Wanxi Peng: Writing - review & editing. Rune
Dietz: Writing - review & editing.
Declaration of Competing Interest
The authors declare that they have no known competing financial
interests or personal relationships that could have appeared to influ-
ence the work reported in this paper.
Acknowledgements
BONUS BALTHEALTH has received funding from BONUS (Art. 185),
funded jointly by the EU, Innovation Fund Denmark (grants 6180-
C. Sonne, et al. Environment International 139 (2020) 105725
7
00001B and 6180-00002B), Forschungszentrum Jülich GmbH, German
Federal Ministry of Education and Research (grant FKZ 03F0767A),
Academy of Finland (grant 311966) and Swedish Foundation for
Strategic Environmental Research (MISTRA). We also thank Henan
Agricultural University and Universiti Malaysia Terengganu under
Golden Goose Research Grant Scheme (GGRG) (Vot 55191) for sup-
porting Dr Lam to perform this review project with Aarhus University.
Appendix A. Supplementary material
Supplementary data to this article can be found online at https://
doi.org/10.1016/j.envint.2020.105725.
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