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Hello Mike, my name is***** and thanks for your question.
When the vehicle is in 2wd there is full vacuum to the front hubs to keep them released. When switching to 4x4 or 4x4 low vacuum is removed to allow the hubs to engage. There should be no difference between 4x4 or 4x4 low as the vacuum routing is the same. I would be more inclined to suspect the misfire goes away in 4x4 low due to the powertrain control module default operating strategy is different then when in 2wd or 4x4 high due to engine load calculations. At his point I would ignore the 4x4 low issue and just concentrate on the misfire itself.
At this point you need to have the powertrain control module (PCM) tested for codes to see which cylinder is misfiring or if the PCM is going into load limiting strategy due to a fault from an input in the system.
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These engines are notorious for loaded engine misfires from the spark plugs breaking down under load. How many miles on the spark plugs?