  Primordial non-Gaussianity (PNG) is a key probe of the origins of primordial
fluctuations in the early universe. It has been shown that multi-tracer
measurements of large-scale structure can produce high-precision measurements
of PNG. Future line intensity mapping surveys are well-suited to these
measurements owing to their ability to rapidly survey large volumes and access
the large scales at which PNG becomes important. In this paper, we explore for
the first time how multi-tracer PNG measurements with intensity mapping surveys
depend on the sub-galactic scale physics which drives line emission. We
consider an example cross-correlation between CO maps, and quantify the impact
varying the astrophysical model has on $f_{\mathrm{NL}}$ measurements. We find
a non-trivial coupling between horizon-scale PNG measurements and the molecular
cloud-scale interstellar medium that can have order unity effects on
$f_{\mathrm{NL}}$ constraints with near-future experimental sensitivities. We
discuss how these effects depend on noise level and survey design. We further
find that the cross-correlation shot noise, an effect nearly unique to
intensity mapping measurements, can play an important role in multi-tracer
analyses and should not be neglected.
