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  Killer whale fibroblasts were exposed to pollutants (POPs) and morbillivirus (CeMV).

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  The killer whale fibroblasts supported the replication of CeMV.

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  POP exposure led to a decrease in cell viability and an increase in CeMV replication.

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  Fibroblasts show potential as a model for pathogen–pollutant co-exposure studies.

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  Results suggest POP exposure may increase the severity of viral infection in cetaceans.

Killer whales (Orcinus orca) accumulate high levels of persistent organic pollutants (POPs), which have been linked to immunomodulation. Over the past decades, large-scale mortality events associated with cetacean morbillivirus (CeMV) have affected cetacean populations, and concerns have been raised about the role of contaminants in exacerbating these outbreaks. However, establishing cause-effect relationships in free-roaming cetaceans remains a significant challenge. In vitro approaches present unique potential for furthering our understanding of the effects of multiple environmental stressors in marine mammal health. In this study, we used primary fibroblasts cultured from wild Norwegian killer whale skin biopsies (n = 6) to assess how exposure to POP mixtures affects cell viability and CeMV replication. Our findings demonstrate that CeMV successfully replicates in killer whale fibroblasts, with the viral replication significantly increasing over the duration of the experiment. POP exposure led to a concentration-dependent decrease in cell viability and a significant increase in viral replication. These results validate killer whale primary fibroblasts as a valuable in vitro tool for the study of co-exposure of POPs and morbillivirus on toothed cetaceans. Moreover, these findings support the need for further research to confirm the role of contaminants in intensifying the severity of CeMV infections in the wild.