Weddell (Leptonychotes weddellii), Ross (Ommatophoca rossii) and crabeater seals (Lobodon carcinophaga) are phocid seals with a circumpolar distribution around Antarctica. As long-lived and large top predators, they bioaccumulate contaminants and are considered as sentinels of ecosystem health. Antarctic seals are increasingly exposed to climate change, pollution, shipping and fisheries. To reveal and understand possible anthropogenic impacts on their immune and health status, this study investigates sensitive biomarkers of the xenobiotic metabolism and immune system in relation to mercury (Hg) burden. Gene-transcription studies using minimally-invasive blood samples are useful to monitor physiological processes in wildlife that can be related to different stressors. Blood samples of 72 wild-caught seals (Weddell n=33; Ross n=12; crabeater n=27) in the Amundsen and Ross Seas in 2008-2011 were investigated. Copy numbers per µl mRNA transcription of xenobiotic biomarkers (aryl hydrocarbon receptor (AHR)), aryl hydrocarbon receptor nuclear translocator (ARNT) and peroxisome proliferator-activated receptor (PPARa) and immune relevant cell mediators (cytokines interleukin-2 (IL-2), interleukin-10 (IL-10) and heat-shock-protein 70 (HSP70)) were measured using reference genes Tyrosine 3-monooxygenase/tryptophan 5-monooxygenase activation protein, zeta polypeptide (YWHAZ) and ribosomal protein L4 (RPL4) by real time RT-qPCR. Hg concentration was analysed in fur. Hg concentration increased with body weight and standard length in all species. Crabeater seals showed a lower Hg concentration than Ross and Weddell seals. Species-specific differences in gene-transcription were found between all species with highest levels of AHR, ARNT and PPARa in crabeater seals. Ross seals showed highest IL-10 and HSP70 transcription, while HSP70 was exceptionally low in crabeater seals. Between Hg and HSP70 a clear negative relationship was found in all species. The species-specific, age and sex-dependent gene-transcription probably reflect dietary habits, pollutant exposure and immune status.