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bioRxiv · 10.64898/2026.02.09.704935

Phthalate exposure induces inflammatory signaling and alters mitochondrial respiration in marine mammal and human cells

Piotrowski, E. R.·Lam, E. K.·Moreno-Santillan, D. D.·Allen, K. N.·Crocker, D. E.·Goksoyr, A. E.·Vazquez-Medina, J. P.
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Abstract

This study investigated the transcriptional and bioenergetic responses to monoethylhexyl phthalate (MEHP) in primary fibroblasts derived from northern elephant seals (Mirounga angustirostris), common dolphins (Delphinus delphis), and humans, using RNA-seq, extracellular flux assays, and high-resolution microscopy of the mitochondrial reticulum. MEHP exposure did not induce cytotoxicity but triggered species-specific changes in gene expression and mitochondrial metabolism and morphology. Human cells showed the greatest transcriptional response, upregulating genes involved in detoxification, antioxidant, and inflammation while downregulating lipid metabolism pathways. The highest dose also decreased mitochondrial respiration and increased mitochondrial fragmentation, triggering a metabolic shift toward glycolysis. Elephant seal cells showed delayed glycolytic shifts, maintaining mitochondrial respiration and upregulating antioxidant, immune, and metabolic pathway genes through the highest dose. Despite mitochondrial fragmentation, they upregulated mitochondrial fusion/fission and trafficking genes. Dolphin cells exhibited the fewest changes in gene expression, mostly in hormone signaling and mitotic pathways. They showed dose-dependent declines in both respiration and glycolytic rates, even at the lowest concentration, yet maintained mitochondrial structural integrity while upregulating stress- and hypoxia-induced genes. These distinct strategies highlight species-specific susceptibility to toxicant-induced stress, offering new insights into how marine mammals respond to plastic-derived contaminants and reinforcing the need for species-specific ecotoxicological risk assessments.

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Piotrowski, E. R., Lam, E. K., Moreno-Santillan, D. D., Allen, K. N., Crocker, D. E., Goksoyr, A. E., Vazquez-Medina, J. P.. 2026-02-11. Phthalate exposure induces inflammatory signaling and alters mitochondrial respiration in marine mammal and human cells. https://doi.org/10.64898/2026.02.09.704935

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