Transcriptomics and stress indices reveal Tetraglyme-mediated adverse effects in the Mediterranean mussel Mytilus galloprovincialis

The present study provides the first integrated assessment of tetraethylene glycol dimethyl ether (Tetraglyme) on the Mediterranean mussel Mytilus galloprovincialis, by combining cellular, oxidative, and genotoxic stress indices along with transcriptomic profiling. Our findings represent the first molecular and physiological evidence of Tetraglyme-induced toxicity in a marine invertebrate. Mussels were exposed to environmentally relevant concentrations of Tetraglyme (1-1000 μg L^-1) for four days (Tetra-mussels) and showed increased hemocyte lysosomal membrane destabilization (in terms of lower neutral red retention time/NRRT values), higher frequencies of nuclear abnormalities (micronuclei and total nuclear abnormalities), and elevated oxidative-stress indices (NO₂^-, O₂^·- and MDA) at concentrations higher than 1 μg L⁻¹ . In parallel, transcriptome analysis of gill tissue revealed extensive differential expression of genes involved in cell homeostasis, metabolism, detoxification, cell signaling, apoptosis, and immune function. Notably, most high-confidence genes were downregulated, highlighting a pervasive molecular response and potential impairment of vital biological processes. Our results underscore the importance of multi-endpoint, omics-informed approaches for early detection of chemical threats to aquatic biodiversity and contribute novel mechanistic insight for the protection of aquatic ecosystems.