The sea lice Caligus elongatus and Lepeophtheirus salmonis are both causing problems in salmonid aquaculture. Since the salmonid specialist L. salmonis represents the dominating problem, research on host-parasite interactions has focused on L. salmonis and Atlantic salmon (Salmo salar), while less is known for the generalist C. elongatus. As new knowledge can be found in the comparison between a specialist and a generalist, the present study compares the salmon immune responses and louse modulatory proteins between C. elongatus and L. salmonis. While the severity of skin lesions inflicted underneath both lice species appeared similar, C. elongatus seemed to be better at dampening inflammatory responses than L. salmonis. A comparison of exocrine gland genes encoding proteins with known effect at the host-parasite interface showed that C. elongatus express most of the genes previously identified in L. salmonis. Interestingly, three orthologues of the labial gland protein 3 (LGP3) known to induce cell death in salmonid immune cells were found. This expansion of the LGP3 gene might explain the limited influx of immune cells observed underneath C. elongatus, though yet unknown C. elongatus specific glandular proteins might also be at play. Despite the limited inflammatory response induced by adult C. elongatus, they provoke a forceful host anti-lice behaviour that is comparably less prominent in salmon infested with L. salmonis. Setule-like processes identified on the ventral surface of the C. elongatus marginal membrane might be of importance here, as could species specific behavioural differences or differences in the host modulatory proteins.