As long-lived marine mammals found throughout the temperate coastal waters of the North Pacific and Atlantic Oceans, harbour seals (Phoca vitulina) have become an invaluable sentinel of food-web contamination. Their relatively high trophic position predisposes harbour seals to the accumulation of harmful levels of persistent organic pollutants (POPs). We obtained skin/blubber biopsy samples from live-captured young harbour seals from various sites in the northeastern Pacific (British Columbia, Canada, and Washington State, USA) as well as the northwestern Atlantic (Newfoundland and Quebec, Canada). We developed harbour seal-specific primers to investigate the potential impact of POP exposure on the expression of eight important genes. We found correlations between the blubber mRNA levels of three of our eight target genes and the dominant persistent organic pollutant in seals [polychlorinated biphenyls (PCBs)] including estrogen receptor alpha (Esr1: r 2 = 0.12, p = 0.038), thyroid hormone receptor alpha (Thra: r 2 = 0.16; p = 0.028), and glucocorticoid receptor (Nr3c1: r 2 = 0.12; p = 0.049). Age, sex, weight, and length were not confounding factors on the expression of genes. Although the population-level consequences are unclear, our results suggest that PCBs are associated with alterations of the expression of genes responsible for aspects of metabolism, growth and development, and immune function. Collectively, these results provide additional support for the use of harbour seals as indicators of coastal food-web contamination.