Metabolomics measures low molecular weight endogenous metabolites and changes linked to contaminant exposure in biota. Few studies have explored the relationship between metabolomics and contaminants in Arctic wildlife. We analyzed 239 endogenous metabolites and ∼150 persistent organic pollutants (POPs), including total mercury (THg), in the liver of polar bears and their ringed seal prey harvested from low Canadian Arctic (western Hudson Bay; WHB) and high Arctic (HA) locations during 2015-2016. Polar bears from the HA had different metabolomic profiles compared to those from WHB, particularly in several phosphatidylcholines (PCs), with the HA bears having higher concentrations of longer chain PCs. Similarly, HA and WHB ringed seals also had metabolomic profile differences in five PCs related to fat catabolism and transport. The metabolites with the highest impact on discriminating metabolomic profiles between the two species, based on VIP scores, were: tauroursodeoxycholic Acid (TUDCA), histamine, serotonin, lithocholic acid (LCA), and taurolithocholic acid (TLCA). Higher TUDCA levels in polar bears likely reflect their blubber-rich diet, while higher histamine in seal liver may indicate inflammatory responses. Significant correlations were found between liver metabolites and several per- and polyfluoroalkyl substances (PFAS) in both species, including PFOA, PFNA, PFDA, PFEtCHxS, PFOS, and/or PFDS that moderately correlated to PCs. THg in seals and bears was negatively correlated with sarcosine. This study revealed significant correlations and differences in metabolite profiles of polar bears and ringed seals, suggesting that PFAS impacted several pathways related to lipid metabolism, bile acid synthesis, antioxidant defenses, arginine biosynthesis, histidine metabolism, and sphingolipid metabolism, with ringed seals showing greater sensitivity to PFAS. These results indicate that PFAS may influence metabolic processes in Arctic wildlife, although further research is needed to understand the full impact on Arctic wildlife health.
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