Martina Leonessi, Manon Auguste, Lapo Doni, Teresa Balbi, Luigi Vezzulli, Laura Canesi
Marine bivalves are increasingly threatened by disease outbreaks and mass mortality events driven by climate change and polymicrobial infections. Mytilus galloprovincialis is the main farmed bivalve in the Mediterranean, one of the world's fastest-warming marine regions, with the Ligurian Sea experiencing particularly rapid increases in temperature and heatwave frequencies and intensities. Bivalve hemocytes integrate environmental and microbial cues, making their seasonal dynamics a key determinant of host resilience under changing climate conditions. Previous studies identified surface seawater temperature (SST) as the main environmental driver of gametogenesis, immunocompetence, and hemolymph microbiota in mussels from the Ligurian Sea. Here, we monthly monitored immune function, immune gene expression, and hemolymph microbiota in mussels from the same site in 2025 and compared the data with those from 2015 and 2020. To assess seasonal immune specificity, hemocytes were also challenged with three bacterial species differing in pathogenicity. The positive relationship previously observed among SST, hemocyte lysosomal membrane stability and Vibrio abundance was no longer detected in 2025, revealing a decoupling of environmental, physiological, and microbial dynamics along with progressive regional warming. Cellular responses to bacterial challenge showed seasonal specificity, that were partially buffered by soluble serum factors, resulting in total bactericidal activity independent of SST. Our findings indicate that ongoing Mediterranean warming is reshaping seasonal immune regulation and host-microbiota interactions in mussels, highlighting the importance of long-term monitoring for predicting biological responses to climate change. The reorganization of immune dynamics may alter host resilience to opportunistic bacterial infections and increase vulnerability to future disease outbreaks.