Abstract Recent studies have revealed integral and complex relationships between hosts and their symbionts. Some of these findings demonstrate that symbionts can affect the gene expression of their hosts. We used a model cleaning symbiosis system of crayfish and their branchiobdellidan symbionts to examine whether symbionts could affect host gene expression through indirect means, by changing the interaction of the host crayfish with the environment. Previous research has shown this symbiosis to be a complex, context dependent relationship in which outcomes can shift between mutualism, when branchiobdellidans act as cleaners of their hosts, and parasitism, when damage to hosts’ gills through branchiobdellidan feeding produces negative effects. These shifts are known to occur with changes in symbiont densities and environmental conditions. We manipulated densities of branchiobdellidans on host crayfish and examined the effect on expression of 3 candidate immune genes. We had 2 competing working hypotheses: 1) That branchiobdellidans would cause an increase expression in immune genes because of damage to the hosts’ gills; 2) That branchiobdellidans would decrease expression of immune genes by acting as cleaners and thus alleviating environmental stress. We found that the second hypothesis was strongly supported when branchiobdellidan activity decreased expression in 2 of the 3 candidate genes. One of these genes (astacidin) was related to generalized immune defense, while the other (prophenoloxidase) is a key part of the melanization cascade that provides defense in the case of physical damage and intrusion of microbes or foreign bodies. Given that there is no known mechanism through which branchiobdellidans can directly affect host physiology through chemical or genetic interactions, we concluded that this alteration in gene expression occurred through alleviation of environmental stress by the symbionts. Such indirect effects may be common in nature and continued study using easily manipulated systems like the crayfish-branchiobdellidan symbiosis may continue to produce insights regarding the importance of symbioses in ecological systems.