Microbial communities are shaped by interspecies chemical signalling and competitive interference through quorum-sensing (QS) molecules. Remarkably, although the concept of QS first originated from work done on the marine symbiont Aliivibrio fischeri, very little is known about cell-cell communication in the marine ecosystem. Marine sponges (Porifera) represent a rich chemical reservoir of natural bioactive compounds and understanding how QS operates in this niche would be an important ecological and translational advance. While more often viewed in the context of human disease and infection, Pseudomonas aeruginosa and Vibrionaceae species have been isolated from marine sponges sourced off the coast of Ireland. Here, we investigate the antibacterial effects of the P. aeruginosa QS signal 2-heptyl-4-quinolone (HHQ) against members of the Vibrionaceae family. Initial assays revealed that HHQ activity against Vibrio species is not binary but operates along a susceptibility gradient. While Aliivibrio fischeri was completely inhibited at low HHQ concentrations, species such as V. alginolyticus and V. diabolicus tolerated levels up to 100 µM. Comparative genomics revealed a second cydAB operon in V. parahaemolyticus, also present in P. aeruginosa. However, deletion of the cydAB genes did not sensitize the strain to 10 µM HHQ. Supernatant cross-feeding assays suggest an inducible, cell-associated mechanism of sequestration and/or detoxification, while prolonged exposure of V. scophthalmi to HHQ led to the emergence of spontaneous resistant mutants, indicating the potential for adaptive resistance under sustained selective pressure. Our findings reveal that HHQ functions as a species-specific antimicrobial in marine environments, with species-level tolerance evident in Vibrionaceae.