Abstract We model natural selection for or against an anti-parasite (or anti-predator) defense allele in a host (or prey) population that is structured into many demes. The defense behavior has a fitness cost for the actor compared to non defenders (“cheaters”) in the same deme and locally reduces parasite growth rates. Hutzenthaler et al. (2022) have analytically derived a criterion for fixation or extinction of defenders in the limit of large populations, many demes, weak selection and slow migration. Here, we use both individual-based and diffusion-based simulation approaches to analyze related models. We find that the criterion still leads to accurate predictions for settings with finitely many demes and with various migration patterns. A key mechanism of providing a benefit of the defense trait is genetic drift due to randomness of reproduction and death events leading to between-deme differences in defense allele frequencies and host population sizes. We discuss an inclusive-fitness interpretation of this mechanism and present in-silico evidence that under these conditions a defense trait can be altruistic and still spread in a structured population.