Infection response and other immunity-linked genes (ILGs) were first named in Caenorhabditis elegans-based expression after pathogen challenge, but many are also up-regulated when lipid metabolism is perturbed. Why pathogen attack and metabolic changes both increase ILGs is unclear. We find that ILGs are activated when phosphatidylcholine (PC) levels change in membranes of secretory organelles in C. elegans. RNAi targeting of the ADP-ribosylation factor arf-1, which disrupts the Golgi and secretory function, also activates ILGs. Low PC limits ARF-1 function, suggesting a mechanism for ILG activation via lipid metabolism, as part of a membrane stress response acting outside the ER. RNAi of selected ILGs uncovered defects in the secretion of two GFP reporters and the accumulation of a pathogen-responsive complement C1r/C1s, Uegf, Bmp1 (CUB) domain fusion protein. Our data argue that up-regulation of some ILGs is a coordinated response to changes in trafficking and may act to counteract stress on secretory function.