Marma-detox: Whales and polar bear in a petri dish: decoding marine mammal toxicology through in vitro and in silico approaches

Abstract

Arctic marine ecosystems, home to top predators like whales and polar bears, are threatened by bioaccumulative pollutants. Fin whales accumulate phthalates [1], while killer whales and polar bears accumulate PFAS and legacy POPs [2,3]. Due to challenges in studying these species in the wild, the Marma-detox project (NFR no. 334739) establishes in vitro models to explore marine mammal toxicology. Primary cells were isolated from biopsies of whales and polar bears. A luciferase reporter assay showed that phthalates modulate PPARG, THRB, and GR activity in fin whales. RT-qPCR analysis of phthalate-exposed fin whale fibroblasts revealed higher sensitivity of the GR pathway compared to PPARG and THRB. Killer whale fibroblasts were exposed to PFAS to investigate effects on lipid metabolism. However, low pparg and ppara expression in whale fibroblasts limits their utility for such studies. Killer whale fibroblasts were used to assess broader PFAS effects on metabolism and cell state. Preliminary findings indicate that directly converting primary cells into adipocytes offers a more suitable model for studying pollutant impacts on lipid metabolism. Overall, these cell-based models, together with in silico analyses, provide valuable insight into the molecular mechanisms of pollutant toxicity, offering a tool for assessing environmental risks in vulnerable Arctic species.