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

Abstract

Background: Whales and polar bears are important mid or top predators in arctic marine ecosystems, which face sustained levels of contaminants with bioaccumulating and biomagnifying properties. Notably, Killer whales experience a significant burden of these pollutants potentially threatening their reproductive abilities. Despite the ecological importance of these species, a mechanistic understanding of contaminant responses in these marine animals is hampered by the challenges of studying them in their natural habitats. Addressing this, the Marma-detox project adopts an innovative in vitro and in silico approach to unravel the intricacies of marine mammals' toxicological defense systems. The Marma-detox project is driven by the following key objectives: I. Establish fundamental knowledge regarding the genomic underpinnings of toxicological defense systems in specific marine mammal species. II. Characterize the functional properties of crucial molecular targets responsive to environmental contaminants within these species. III. Examine toxicological responses in marine mammal mesenchymal stem cells (MSC) and fibroblast cell lines. IV. Integrate in silico and in vitro findings with existing data on associations between contaminant exposure, biomarkers, and omics data in free-ranging animals. Expected outcomes: The Marma-detox project aspires to yield valuable insights into the toxicological responses of marine mammals, elucidating their "chemical defensome." This defensome encompasses an array of transcription factors, transporters, and antioxidant enzymes working synergistically to detoxify and eliminate harmful compounds, including environmental contaminants. The project stands as a founding collaboration across marine mammal science, environmental chemistry, bioinformatics, and molecular toxicology. By deepening our understanding of marine mammal toxicology, the project aims to expand the frontiers of marine mammal biology, toxicology, and conservation, shedding light on the evolutionary and individual adaptations of these animals. Expected impacts: Beyond its immediate contributions, the Marma-detox project holds broader significance. The methodologies and techniques under development have the potential for transferability to other environmentally susceptible and under-studied wildlife within the field of environmental toxicology. Thus, the project not only intends to advance our knowledge of marine mammal toxicology but also offers tools and insights applicable to the broader context of wildlife conservation and environmental health.