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Exposure levels of persistent organic pollutants, such as polychlorinated biphenyls and DDTs, are high in Arctic apex predators and Inuit peoples and are suspected to have negative impacts on their immune systems. We conducted a controlled generational study on liver tissue and ethylenediaminetetraacetic acid blood cytokine and acute-phase protein (APP) mRNA expressions using reverse transcriptionase-polymerase chain reaction in West Greenland sledge dogs (Canis familiaris); contaminated minke whale (Balaenoptera acutorostrata) blubber serves as dietary pollutant source. Two of seven blood cytokine expressions (IL-6 and IL-12) and three of five APP expressions (haptoglobin [HP], heat shock protein, and fatty acid-binding protein [FABP]) were lowest in the exposed group, whereas the remaining five blood cytokine expressions (IL-2, IL-10, IFN-gamma, TNF-alpha, and TGF-beta) and two APP expressions (MT1 and MT2) were highest in the exposed group. In liver tissue, three cytokine expressions (IL-10, IFN-gamma, and TNF-alpha) and two APP expressions (MT1 and MT2) were highest in the exposed group, and the remaining cytokine and APP expressions were lowest in the exposed group. Of these, the liver tissue expression of HP and FABP was significantly lowest in the exposed group (both p < 0.05). As a consequence of our findings, we suggest that a daily intake of 50 to 200 g polluted whale blubber is associated with a genotoxic decrease in HP and FABP gene expression in the liver of sledge dog and possibly of other top mammalian marine predators and consumers in the Arctic, indicating a restricted acute-phase reaction and insufficient immune response. Finally, HP and FABP liver expression appear to be new and sensitive biomarkers of organohalogen compound exposure.