Is a Commensal Here, a Pathogen There? Genotype Specific Responses by the Sea Anemone Nematostella vectensis to...

Animals rely on diverse molecular mechanisms to maintain beneficial microbial associations while also defending against pathogens, yet the extent to which these responses vary among genotypes of a single species remains poorly understood. Using individuals from different locations of the sea anemone Nematostella vectensis, we compared transcriptional responses to a commensal (Vibrio diabolicus) and pathogen (Vibrio coralliilyticus) bacterium. We find striking genotype-specific divergence: individuals from Nova Scotia mounted a strong transcriptional response to V. diabolicus, whereas the North Carolina and Florida individuals showed almost no response to this same bacterium. In contrast, all individuals regardless of location exhibited a large transcriptional response to the pathogen V. coralliilyticus. These responses involved key immune pathways (e.g., cGAS-STING, NF-κB, and proteostasis-related stress responses), suggesting that different genotypes deploy distinct molecular responses when encountering the same bacterium. The robust, immune-like response of the individuals from Nova Scotia to a bacterium considered commensal in other populations indicates that V. diabolicus may not function as a commensal across the species range. Such genotype-by-microbe specificity points to potential local adaptation to particular bacterial partners that underscores the complexity of holobiont regulation across heterogeneous environments and stresses the importance of assessing additive, synergistic, and antagonistic interactions across hologenomic mosaics.